Human monoclonal antibodies against tetanus toxoid

• Grant number: 12/14127-0
• Support Opportunities: Regular Research Grants
• Duration: October 01, 2012 - September 30, 2015
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Ana Maria Moro
• Grantee: Ana Maria Moro
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated researchers: Silvia Beatriz Boscardin

Abstract

Antibodies, being specific in their antigen binding and capable of neutralization, have been used since the beginning of 20th century for treatment of various infectious diseases, including pneumococcal pneumonia, meningococcal meningitis, erysipelas, anthrax and others (Casadevall and Scharff, 1994; Casadevall and Scharff, 1995). Serum-therapy was established as a powerful tool for the control of infectious diseases and, until today, antibodies remain as the only therapeutic option for the neutralization of venoms and bacterial toxins. The majority of the available antidote preparations derive from heterologous sources. Among them, there is the anti-tetanus antibodies' preparation. Tetanus is a disease caused by the C. tetani toxin. Prophylaxis is maintained by the vaccination against tetanus toxoid. To deal with accidents caused by the C.tetani the hyperimmune sera produced by horses immunization is available and effective. However, the use of heterologous proteins can elicit immunogenicity reactions, lowering the efficacy and also preventing possible future treatments. Aiming to offer a better product, we propose in this study the development of human monoclonal antibodies for the control of tetanus toxoid infection. For that we will make use of an innovative protocol developed at Dr. Nussenweig's laboratory (Rockefeller University) (Wardemann et al., 2003), based on the sorting of specific memory B cells present in the peripheral blood of immunized individuals. The success of the project will allow us to plan, in the future, to express these antibodies in conditions for clinical studies. (AU)